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J M Andrews

Publications and source records attributed to J M Andrews.

At least 37 records · Page 2Linked to original sources
PubMed2002

In vitro activities of peptide deformylase inhibitors against gram-positive pathogens.

The activities of six peptide deformylase (PDF) inhibitors against 107 respiratory tract pathogens were studied and compared to those of ciprofloxacin and amoxicillin-clavulanate. Against Streptococcus pneumoniae, BB-83698 and BB-83815 were the most active PDF inhibitors (MIC at which 90% of the organisms tested were inhibited [MIC(90)], 0.25 microg/ml). Five of the agents showed similar activity against Moraxella catarrhalis (MIC(90), 0.12 microg/ml). All PDF inhibitors were less active against Haemophilus influenzae; BB-3497 was the most active agent (MIC(90), 2 microg/ml). Five agents were studied against Chlamydia spp. and showed activity similar to that of ciprofloxacin (MIC, 0.5 to 4 microg/ml). This study demonstrates that PDF inhibitors have the potential to be developed for the treatment of respiratory tract infections.

Amidohydrolases↗
PubMed2001

Effect of a lacto-ovo vegetarian diet on fasting small intestinal motility.

BACKGROUND: Changes in diet can alter gastric and small intestinal (SI) motility. The effects of a vegetarian diet on fasting SI motility are unknown. METHODS: Manometric studies were performed in 9 lacto-ovo vegetarians (7 women) and 9 omnivores (7 women) of similar age and body mass index. On each study day, manometry was used to assess SI motility for 5 h, or 3 complete cycles of the interdigestive motor complex (IDMC). Lacto-ovo vegetarians were studied once: omnivores were studied twice, on their usual diet, and after consuming a 14-day lacto-ovo vegetarian diet. Diet diaries were kept for 5 days prior to each manometric study. Data were analysed for dietary composition and for cycle length and duration of each phase (I, II and III) of the IDMC. RESULTS: Dietary intake did not differ between chronic vegetarians and chronic omnivores apart from a trend to higher fibre intake (29 +/- 3 versus 20 +/- 3 g/day; P = 0.058). Omnivores eating a vegetarian diet showed a trend to decreased alcohol consumption (P = 0.068), but did not increase their fibre intake (20 +/- 3 versus 21 +/- 3 g/day). Neither cycle length nor duration of each IDMC phase differed between chronic vegetarians and chronic omnivores. After 14 days of a vegetarian diet, omnivores had a reduction in cycle length (128 +/- 19 versus 86 +/- 12 min; P = 0.02), with a non-significant reduction of Phase II (99 +/- 20 versus 50 +/- 8 min: P = 0.066). CONCLUSIONS: A chronic vegetarian diet has no major effect on fasting SI motility; but acute dietary change may alter the cycle length and component phases of the IDMC.

Adolescent↗
PubMed2001

Pharmacokinetics and tissue penetration of gemifloxacin following a single oral dose.

The pharmacokinetics and tissue penetration of gemifloxacin were determined during a 24 h period following oral administration of a single 320 mg dose to each of 10 healthy male volunteers. Concentrations of the drug in plasma, inflammatory blister fluid and urine were determined using a microbial assay. A peak plasma concentration (mean +/- S.D.) of 2.33 +/- 0.5 mg/L was reached at 1.20 +/- 0.4 h. Mean penetration into inflammatory fluid was 61.19 +/- 10.4%. A peak concentration of 0.74 +/- 0.3 mg/L was reached in the inflammatory fluid at a mean time of 3.40 +/- 1.7 h. The mean elimination half-life from serum and inflammatory fluid was 5.94 +/- 0.4 and 6.27 +/- 2.4 h, respectively. Urinary excretion of the drug at 24 h post-dose was 36.11% of the total given. These results demonstrate that gemifloxacin penetrates into the site of inflammation and reaches sufficient concentrations to inhibit many pathogens.

Administration, Oral↗
PubMed2001

Lung concentrations of telithromycin after oral dosing.

Concentrations of telithromycin were measured in plasma, bronchial mucosa (BM), epithelial lining fluid (ELF) and alveolar macrophages (AM) following multiple oral doses. Concentrations were determined using a microbiological assay. There were 20 subjects in the study, allocated to three nominal time periods: 2, 12 and 24 h. Mean concentrations in plasma, BM, ELF and AM for 2, 12 and 24 h were as follows: 2 h, 1.86 mg/L, 3.88 mg/kg, 14.89 mg/L and 69.32 mg/L; 12 h, 0.23 mg/L, 1.41 mg/kg, 3.27 mg/L and 318.1 mg/L; and 24 h, 0.08 mg/L, 0.78 mg/kg, 0.97 mg/L and 161.57 mg/L. These concentrations of telithromycin in BM and ELF exceeded for 24 h the mean MIC90s of the common respiratory pathogens Streptococcus pneumoniae (0.12 mg/L) and Moraxella catarrhalis (0.03 mg/L), as well as the atypical microorganism Mycoplasma pneumoniae (0.001 mg/L), and suggest that telithromycin may be effective for the treatment of community-acquired pneumonia and chronic obstructive pulmonary disease.

Administration, Oral↗
PubMed2001

Activity of daptomycin against Gram-positive pathogens: a comparison with other agents and the determination of a tentative breakpoint.

The in vitro activity of daptomycin was studied in comparison with other agents active against 328 recent clinical isolates of Gram-positive pathogens. MIC data showed that the addition of calcium ions to a final concentration of 50 mg/L enhanced the activity of daptomycin generally by eight- to 16-fold. In the presence of calcium ions daptomycin was uniformly active against the strains of Staphylococcus spp. and Streptococcus spp. studied with a MIC90 of < or = 1 mg/L. Enterococcus faecalis and Enterococcus faecium were slightly less susceptible (MIC90 2 mg/L). Vancomycin-, fluoroquinolone- and quinupristin/dalfopristin-resistant strains were all susceptible to daptomycin. The presence of serum reduced the apparent activity of daptomycin to only a moderate extent. Employing the BSAC methodologies, a tentative breakpoint of 2 mg/L for daptomycin is proposed.

Anti-Bacterial Agents↗
PubMed2001

The development of the BSAC standardized method of disc diffusion testing.

The BSAC Working Party on Susceptibility Testing has developed a standardized method of disc susceptibility testing that has been 'field tested' in 19 diagnostic laboratories in the UK and Ireland. The method employs semi-defined media, a semi-confluent inoculum and relates zones of inhibition with BSAC-specified MIC breakpoints to interpret susceptibility. The bacteria selected for the trial included clinical isolates and control strains from the ATCC and NCTC national collections. Organisms were chosen because they had known attributes, such as being fully susceptible or having a demonstrated mechanism of resistance. The results from this survey are very encouraging. With the commonly isolated Enterobacteriaceae, specifically Escherichia coli, Proteus mirabilis and Klebsiella spp., no major problems were observed except with gentamicin and cefuroxime. In the case of gentamicin, problems were associated with resistant strains of P. mirabilis, with MICs of 2 mg/L, being falsely reported as susceptible. For cefuroxime, it is not unexpected that results were unreliable, as the MIC distribution straddles the in vitro breakpoint concentration (following the results of this study the MIC and zone diameter breakpoints have been amended to improve reporting). No major problems were encountered for Pseudomonas aeruginosa with the agents studied. The 'field survey' has shown that disc testing is unreliable for determining the susceptibility of coagulase-negative staphylococci to teicoplanin, and that the detection of glycopeptide resistance in enterococci is improved by incubation for a full 24 h. Inconsistencies observed with fastidious organisms were associated with incorrect inocula. Zone diameter data for the control strains studied provide information that can be utilized by diagnostic laboratories to monitor the daily performance of testing.

Anti-Bacterial Agents↗
PubMed2001

BSAC standardized disc susceptibility testing method.

For nearly a decade microbiologists have used the MIC breakpoints published in the BSAC Guide to Susceptibility Testing to interpret susceptibility. Historically, and unlike the rest of Europe, the UK and Ireland have used a comparative method of disc testing to interpret susceptibility rather than one based on a correlation between MIC and zone of inhibition. Although innovative when introduced in the 1970s, Stokes' comparative method has evolved ad hoc and it has become increasingly apparent that there is a need for a standardized method of disc testing that is correlated with BSAC MIC breakpoints. The method described here, like all other standardized methods of disc testing, cannot be adapted by the user, and interpretative criteria are only applicable if the method is adhered to fully. A major advantage of this approach to susceptibility testing is that data from several sources can be combined for surveillance of resistance, a task that has been made much easier by the introduction of this method and coincides with the availability of automated zone measuring devices. It is hoped that the method described here will provide the core document for standard operating procedures; however, changes will necessarily occur over time as the method is developed and refined.

Anti-Bacterial Agents↗
PubMed2001

Determination of minimum inhibitory concentrations.

Minimum inhibitory concentrations (MICs) are defined as the lowest concentration of an antimicrobial that will inhibit the visible growth of a microorganism after overnight incubation, and minimum bactericidal concentrations (MBCs) as the lowest concentration of antimicrobial that will prevent the growth of an organism after subculture on to antibiotic-free media. MICs are used by diagnostic laboratories mainly to confirm resistance, but most often as a research tool to determine the in vitro activity of new antimicrobials, and data from such studies have been used to determine MIC breakpoints. MBC determinations are undertaken less frequently and their major use has been reserved for isolates from the blood of patients with endocarditis. Standardized methods for determining MICs and MBCs are described in this paper. Like all standardized procedures, the method must be adhered to and may not be adapted by the user. The method gives information on the storage of standard antibiotic powder, preparation of stock antibiotic solutions, media, preparation of inocula, incubation conditions, and reading and interpretation of results. Tables giving expected MIC ranges for control NCTC and ATCC strains are also supplied.

Anti-Bacterial Agents↗
PubMed2001

Nutrient-induced spatial patterning of human duodenal motor function.

The spatiotemporal patterning of duodenal motor function has been evaluated comprehensively for the first time in humans, with a novel 21-lumen manometric assembly. In nine young, healthy volunteers (6 male, 3 female), duodenal motility was recorded during fasting and three 45-min intraduodenal (ID) nutrient infusion periods (Intralipid at 0.25, 0.5, and 1.5 kcal/min). Pressures were recorded along the length of the duodenum with an array of 18 sideholes at 1.5-cm intervals. Pressure patterns were compared for the final 20 min of each of the four periods. Compared with fasting, ID lipid was associated with regional variation in pressure wave (PW) sequences, with fewer proximally and more distally; this was not observed during fasting (P < 0.001). During fasting and all rates of lipid infusion, most (87-90%) PW sequences were short (1.5-4.5 cm), with a small number (2-4%) of 10.5 cm or longer. At all times, antegrade PW sequences occurred more frequently than retrograde sequences over all distances examined (3, 4.5, and >6 cm), and the proportion of antegrade sequences increased with greater PW sequence length (P = 0.0001). Increasing ID lipid rates appeared to produce dose-related suppression of PW sequences (P < 0.001). The frequency and spatial patterning of human duodenal motor function show substantial variability in response to different nutrient delivery rates. These complex patterns are likely to be involved in duodenal modulation of flow and gastric emptying rate.

Adult↗
PubMed2000

Evaluation of the Oxoid Aura image system for measuring zones of inhibition with the disc diffusion technique.

In this study the Oxoid Aura image antibiotic sensitivity test system, used as a stand-alone device, was compared with manual zone measurement and use of a template, for the determination of sensitivities. An overall correlation coefficient of 0.99 was observed for zone diameters measured using the Aura image system and zones measured manually, when the differences between zones were within 3 mm; 5.4% of zones showed a difference in zone diameter between manual and automated measurement of >3 mm. The results obtained using the template method for interpretation were less reliable than zone measurement, with cefuroxime and ampicillin tested against Enterobacteriaceae and Acinetobacter spp. When linked to a laboratory patient database, the bar code and disc identification facilities avoided errors that were associated with manual data entry.

Acinetobacter↗
PubMed2000

The in vitro activity of ABT773, a new ketolide antimicrobial agent.

The in vitro activity of ABT773, a ketolide antimicrobial agent, was investigated and compared with those of seven other antibiotics. Type strains and 733 Gram-positive, Gram-negative and anaerobic isolates of clinical origin and four CHLAMYDIA: isolates were used. The activity of ABT773 was very similar to that of telithromycin, the other ketolide tested. The MIC(90) was < or = 0.5 mg/L for all bacteria examined except methicillin-resistant Staphylococcus aureus, Enterococcus faecalis, Enterococcus faecium, Haemophilus influenzae and BACTEROIDES: spp. The antichlamydial activity of ABT773 was greater than that of telithromycin, erythromycin and ciprofloxacin. Neither an increase in the size of the inoculm nor the addition of human serum had any marked affect on the in vitro activity of ABT773.

Anti-Bacterial Agents↗
PubMed2000

Repression of tax-mediated human t-lymphotropic virus type 1 transcription by inducible cAMP early repressor (ICER) protein in peripheral blood mononuclear cells.

Human T-lymphotropic virus type 1 (HTLV-1) infection causes adult T-cell leukemia and is characterized by long periods of clinical latency with low levels of viral production. Transcription of HTLV-1 is controlled through sequences in the promoter and enhancer regions of the long terminal repeat of the integrated provirus. Important among these sequences are three 21 bp imperfect repeats responsive to the viral oncogenic protein Tax (TRE). Members of the CREB/ATF-1/CREM family of transcription factors bind to TRE-1 and are critical for HTLV-1 transcription. Other less studied family members include the inducible cAMP early repressor (ICER) proteins. ICER proteins lack phosphorylation and activation domains and are potent inhibitors of transcription. The ability of ICER to bind TRE-1 and its effects on HTLV-1 Tax mediated transcription have not been studied in the natural cell targets of the virus, peripheral blood mononuclear cells (PBMC). We show that ICER mRNA levels are low in quiescent PBMC, but rise and remain elevated for up to 18 hr after mitogenic stimulation of these cells. Electrophoretic mobility shift assays using recombinant Tax and ICER demonstrate that ICER binds TRE-1 and that binding is increased in the presence of Tax. Furthermore, over expression of ICER IIgamma suppressed Tax-mediated transcription whereas an anti-sense ICER II plasmid designed to block endogenous ICER enhanced Tax-mediated transcription in activated PBMC. Together our data indicate that ICER inhibits Tax-mediated transcription in activated PBMC and suggest a role for ICER in maintenance of HTLV-1 persistence.

Adult↗